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1.
Medicine (Baltimore) ; 99(27): e20840, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629669

RESUMO

Osteoporosis is reported to be common among Saudi women. Several minerals appear to be important determinants of insulin-like growth factor (IGF), the bioactivity of which regulates bone and mineral metabolism. Here we proposed that mineral status may alter the IGF system among individuals with osteoporosis. This study aims to evaluate the relationships between essential elements and IGF levels among postmenopausal Saudi women with osteoporosis. A total of 128 postmenopausal Saudi women aged ≥50 years old were recruited in this study. Diagnosis of osteoporosis was done by using dual-energy x-ray absorptiometry to determine the bone minerals density (BMD). Serum calcium and phosphate were determined using routine chemical analyzer. Serum Co, Mn, Ni, Cd were measured using inductively coupled plasma mass spectrometry. Serum IGF-1 and IGF-2 were determined using Luminex xMAP. Using stepwise linear regression analysis, only Cd was identified to be significantly associated with IGF1 in osteoporosis, explaining 3% (confidence interval 0.01-0.05; P = 0001) of the variance perceived. Our results suggest that Cd exposure indirectly affects BMD which may increase the risk of osteoporosis in postmenopausal women. Further longitudinal study using a larger sample size is recommended to determine causality of Cd levels and IGF-1.


Assuntos
Fator de Crescimento Insulin-Like II/análise , Fator de Crescimento Insulin-Like I/análise , Minerais/sangue , Osteoporose Pós-Menopausa/sangue , Absorciometria de Fóton , Idoso , Pesos e Medidas Corporais , Densidade Óssea , Cádmio/sangue , Cálcio/sangue , Cobalto/sangue , Estudos Transversais , Feminino , Humanos , Manganês/sangue , Pessoa de Meia-Idade , Níquel/sangue , Fosfatos/sangue , Arábia Saudita
2.
PLoS One ; 15(6): e0235077, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32569271

RESUMO

Proteinuria and hyperphosphatemia are risk factors for cardiovascular disease in patients with chronic kidney disease (CKD). Although the interaction between proteinuria and the serum phosphate level is well established, the mechanistic link between the two, particularly the extent to which this interaction is mediated by phosphate-regulating factors, remains poorly understood. In this study, we examined the association between proteinuria and the serum phosphate level, as well as potential mediators, including circulating fibroblast growth factor (FGF23)/klotho, the 24-h urinary phosphate excretion rate to glomerular filtration rate ratio (EP/GFR), and the 24-h tubular phosphate reabsorption rate to GFR ratio (TRP/GFR). The analyses were performed with data from 1793 patients in whom 24-h urine protein and phosphate, serum phosphate, FGF23, and klotho levels were measured simultaneously, obtained from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Multivariable linear regression and mediation analyses were performed. Total, direct, and indirect effects were also estimated. Patients with high serum phosphate levels were found to be more likely to exhibit greater proteinuria, higher FGF23 levels, and lower klotho levels. The 24-h EP/GFR increased and the 24-h TRP/GFR decreased with increasing proteinuria and CKD progression. Simple mediation analyses showed that 15.4% and 67.9% of the relationship between proteinuria and the serum phosphate level were mediated by the FGF23/klotho ratio and 24-h EP/GFR, respectively. Together, these two factors accounted for 73.1% of the relationship between serum markers. These findings suggest that proteinuria increases the 24-h EP/GFR via the FGF23/klotho axis as a compensatory mechanism for the increased phosphate burden well before the reduction in renal function is first seen.


Assuntos
Fosfatos/sangue , Proteinúria/sangue , Insuficiência Renal Crônica/sangue , Estudos de Coortes , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Taxa de Filtração Glomerular , Glucuronidase/sangue , Humanos , Túbulos Renais/metabolismo , Túbulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Insuficiência Renal Crônica/fisiopatologia , República da Coreia , Resultado do Tratamento
3.
Medicine (Baltimore) ; 99(24): e20401, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541461

RESUMO

Depression may hamper the immune system and nutritional status, which leads to poor outcomes of treatment. It is very common in dialysis patients. There are the numbers of parameters affected by the depression of patients and available studies are not enough to define the association between biological parameters and depression in the dialysis population. The purposes of the study were to find the prevalence of depression and association of it with the biochemical abnormalities in the dialysis patients.The selected battery of tests (clinician-administered questionnaires) were applied to dialysis patients (test cohort, n = 298) and caregivers (control cohort, n = 202) for establishing depression. The demographic and clinical conditions of participants were also collected. Univariate analysis followed by multiple regression analysis was performed for demographical parameters, clinical conditions, and laboratory results for the detection of association of them with depression. The abnormal test considered as more than 2 SD of mean below the normal value. Out of all tests, at least 2 abnormal tests were considered as mild depression. More than half of abnormal parameters among all tests were considered as moderate depression and all abnormal parameters were considered as severe depression.There was a significant difference for all the test between dialysis patients and the caregivers (P < .0001 for all). The half (153 out of 298) of dialysis patients were depressive and clinically asymptomatic. 70 (23%) dialysis patients were mild depressive, 45 (15%) dialysis patients were moderate depressive, and 38 (13%) dialysis patients were severely depressive. Serum phosphate (P = .023), level of parathyroid hormone (P = .021), and urea reduction rate (P = .048) were directly associated with depression.Biochemical abnormalities (serum phosphate level, parathyroid hormone, and urea reduction rate) were independent predictors of depression in the dialysis population.Level of evidence: III.


Assuntos
Depressão/psicologia , Diálise Renal/psicologia , Uremia/terapia , Adulto , Biomarcadores/sangue , Nitrogênio da Ureia Sanguínea , Cuidadores/psicologia , Estudos de Casos e Controles , China/epidemiologia , China/etnologia , Estudos de Coortes , Depressão/sangue , Depressão/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Prevalência , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Uremia/complicações
4.
Medicine (Baltimore) ; 99(20): e20202, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32443343

RESUMO

AIM: Maintenance hemodialysis (MHD) frequency is associated with survival and complication rates. Achieving the optimal balance between healthcare, quality of life (QOL), and medical costs is challenging. We compared complications, inflammatory status, nutritional status, and QOL between patients with different MHD frequencies. MATERIAL AND METHODS: This was a multicenter randomized trial of patients treated between May 2011 and August 2017 at 3 tertiary hospitals in Wenzhou. Patients were grouped according to their treatment schedule over 1 year: twice-weekly or 3-times-weekly. Complications, biochemistry parameters, and QOL (KDQOL-SFTM 1.3 scale) were assessed. RESULTS: One hundred forty patients were included aged 29 to 68 years (mean age, 50.9 ±â€Š4.3 years). There were no significant differences in infection, heart failure, or cerebral hemorrhage complications between the 2 groups (P = .664). Pre-dialysis hemoglobin, high-sensitivity C-reactive protein, serum albumin, total cholesterol, triglyceride, calcium, phosphate, parathyroid hormone, and ejection fraction were similar in both groups (P > .05). After 1 year of MHD, both groups exhibited significant improvements in these parameters (all P < .05) with no significant differences between groups. Serum creatinine, blood urea nitrogen (BUN), and weekly standard hemodialysis treatment adequacy did not improve after treatment (all P > .05), although a difference in BUN was observed between the 2 groups (P < .001). QOL was superior in the twice-weekly group than in the 3-times-weekly group (all P < .05), except for social support, which was slightly better in the 3-times-weekly group than in the twice-weekly group. CONCLUSIONS: Twice- and 3-times-weekly MHD resulted in comparable inflammatory and nutritional clinical outcomes and adverse events. QOL was better for the twice-weekly schedule. Even for patients with economic constraints, twice- or 3-times-weekly MHD should be selected with caution after consideration of BUN levels at baseline.


Assuntos
Falência Renal Crônica/terapia , Diálise Renal/efeitos adversos , Diálise Renal/tendências , Nitrogênio da Ureia Sanguínea , Proteína C-Reativa/análise , Cálcio/sangue , Hemorragia Cerebral/epidemiologia , China/epidemiologia , Colesterol/sangue , Creatinina/sangue , Feminino , Insuficiência Cardíaca/epidemiologia , Hemoglobinas/análise , Humanos , Infecções/epidemiologia , Inflamação/epidemiologia , Masculino , Pessoa de Meia-Idade , Estado Nutricional/fisiologia , Hormônio Paratireóideo/sangue , Fosfatos/sangue , Qualidade de Vida/psicologia , Diálise Renal/economia , Diálise Renal/psicologia , Albumina Sérica , Volume Sistólico/fisiologia , Triglicerídeos/sangue
5.
Eur J Endocrinol ; 183(2): 181-189, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32454455

RESUMO

Objective: Long-term androgen deprivation therapy (ADT) negatively influences bone. The short-term effects on bone and mineral homeostasis are less known. Therefore, we aimed to investigate the early effects of ADT on calcium/phosphate homeostasis and bone turnover. Design: Prospective cohort study. Methods: Eugonadal adult, male sex offenders, who were referred for ADT to the endocrine outpatient clinic, received cyproterone acetate. Changes in blood markers of calcium/phosphate homeostasis and bone turnover between baseline and first follow-up visit were studied. Results: Of 26 screened patients, 17 were included. The median age was 44 (range 20-75) years. The median time interval between baseline and first follow-up was 13 (6-27) weeks. Compared to baseline, an 81% decrease was observed for median total testosterone (to 3.4 nmol/L (0.4-12.2); P < 0.0001) and free testosterone (to 0.06 nmol/L (0.01-0.18); P < 0.0001). Median total estradiol decreased by 71% (to 17.6 pmol/L (4.7-35.6); P < 0.0001). Increased serum calcium (P < 0.0001) and phosphate (P = 0.0016) was observed, paralleled by decreased PTH (P = 0.0156) and 1,25-dihydroxyvitamin D3 (P = 0.0134). The stable calcium isotope ratio (δ44/42Ca) decreased (P = 0.0458), indicating net calcium loss from bone. Bone-specific alkaline phosphatase and osteocalcin decreased (P < 0.0001 and P = 0.0056, respectively), periostin tended to decrease (P = 0.0500), whereas sclerostin increased (P < 0.0001), indicating suppressed bone formation. Serum bone resorption markers (TRAP, CTX) were unaltered. Conclusions: In adult men, calcium release from the skeleton occurs early following sex steroid deprivation, reflecting early bone resorption. The increase of sclerostin and reduction of bone formation markers, without changes in resorption markers, suggests a dominant negative effect on bone formation in the acute phase.


Assuntos
Antagonistas de Androgênios/farmacologia , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/fisiologia , Calcificação Fisiológica/efeitos dos fármacos , Acetato de Ciproterona/farmacologia , Adulto , Idoso , Bélgica , Remodelação Óssea/efeitos dos fármacos , Cálcio/sangue , Estudos de Coortes , Homeostase/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatos/sangue , Estudos Prospectivos , Delitos Sexuais , Testosterona/sangue
6.
JAMA ; 323(5): 432-443, 2020 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-32016310

RESUMO

Importance: Intravenous iron enables rapid correction of iron-deficiency anemia, but certain formulations induce fibroblast growth factor 23-mediated hypophosphatemia. Objective: To compare risks of hypophosphatemia and effects on biomarkers of mineral and bone homeostasis of intravenous iron isomaltoside (now known as ferric derisomaltose) vs ferric carboxymaltose. Design, Setting, and Participants: Between October 2017 and June 2018, 245 patients aged 18 years and older with iron-deficiency anemia (hemoglobin level ≤11 g/dL; serum ferritin level ≤100 ng/mL) and intolerance or unresponsiveness to 1 month or more of oral iron were recruited from 30 outpatient clinic sites in the United States into 2 identically designed, open-label, randomized clinical trials. Patients with reduced kidney function were excluded. Serum phosphate and 12 additional biomarkers of mineral and bone homeostasis were measured on days 0, 1, 7, 8, 14, 21, and 35. The date of final follow-up was June 19, 2018, for trial A and May 29, 2018, for trial B. Interventions: Intravenous administration of iron isomaltoside, 1000 mg, on day 0 or ferric carboxymaltose, 750 mg, infused on days 0 and 7. Main Outcomes and Measures: The primary end point was the incidence of hypophosphatemia (serum phosphate level <2.0 mg/dL) between baseline and day 35. Results: In trial A, 123 patients were randomized (mean [SD] age, 45.1 [11.0] years; 95.9% women), including 62 to iron isomaltoside and 61 to ferric carboxymaltose; 95.1% completed the trial. In trial B, 122 patients were randomized (mean [SD] age, 42.6 [12.2] years; 94.1% women), including 61 to iron isomaltoside and 61 to ferric carboxymaltose; 93.4% completed the trial. The incidence of hypophosphatemia was significantly lower following iron isomaltoside vs ferric carboxymaltose (trial A: 7.9% vs 75.0% [adjusted rate difference, -67.0% {95% CI, -77.4% to -51.5%}], P < .001; trial B: 8.1% vs 73.7% [adjusted rate difference, -65.8% {95% CI, -76.6% to -49.8%}], P < .001). Beyond hypophosphatemia and increased parathyroid hormone, the most common adverse drug reactions (No./total No.) were nausea (iron isomaltoside: 1/125; ferric carboxymaltose: 8/117) and headache (iron isomaltoside: 4/125; ferric carboxymaltose: 5/117). Conclusions and Relevance: In 2 randomized trials of patients with iron-deficiency anemia who were intolerant of or unresponsive to oral iron, iron isomaltoside (now called ferric derisomaltose), compared with ferric carboxymaltose, resulted in lower incidence of hypophosphatemia over 35 days. However, further research is needed to determine the clinical importance of this difference. Trial Registration: ClinicalTrials.gov Identifiers: NCT03238911 and NCT03237065.


Assuntos
Anemia Ferropriva/tratamento farmacológico , Dissacarídeos/efeitos adversos , Compostos Férricos/efeitos adversos , Hematínicos/efeitos adversos , Hipofosfatemia/induzido quimicamente , Maltose/análogos & derivados , Adulto , Anemia Ferropriva/complicações , Biomarcadores/sangue , Biomarcadores/urina , Dissacarídeos/uso terapêutico , Feminino , Compostos Férricos/uso terapêutico , Cefaleia/induzido quimicamente , Hematínicos/uso terapêutico , Humanos , Hipofosfatemia/epidemiologia , Incidência , Masculino , Maltose/efeitos adversos , Maltose/uso terapêutico , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Fosfatos/sangue , Fosfatos/urina
7.
J Steroid Biochem Mol Biol ; 199: 105611, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32007562

RESUMO

Gestational hypercalcemia is associated with an increased risk of maternal, fetal and neonatal morbidity and mortality. Hypercalcemia may develop during pregnancy in individuals who were previously asymptomatic. The increased sensitivity during pregnancy may be related to physiological, gestational alterations in vitamin D and calcium metabolism and may be influenced by gene variants. The prevalence is unknown. We investigated the prevalence of hypercalcemia in trimester 3 (T3) in a population representative prospective cohort study (n = 1832) in South-West Sweden. Women with serum albumin (Alb) adjusted calcium (CaAlb) ≥ 2.65 mmol/L in T3 (n = 30) were matched to normo-calcemic controls, and markers of calcium and vitamin D metabolism were investigated in trimester 1 (T1) and T3. Serum concentrations of Ca, phosphate (P), Magnesium (Mg), Alb and creatinine (Cr), parathyroid hormone (PTH; T3 only), vitamin D metabolites (total 25(OH)D, 1,25(OH)2D, 24,25(OH)2D, and free 25(OH)D) were analysed in T1 and T3. CaAlb (Payne; inter-laboratory difference: UEA = 0.15 + 0.9*UGOT; UEA 2.54 = UGOT 2.65) and estimated glomerular filtration rate (eGFR; modified 4-variable MDRD) and vitamin D metabolites ratios (VMR) were calculated. Normally and non-normally distributed data were presented as mean (SD) or median (95 %CI). Group differences in relationships between vitamin D metabolites and with PTH were investigated with multiple regression analyses. Hypercalcemia in T3 was found in 1.7 % of women. PTH concentrations suggestive of primary hyperparathyroidism was found in 1 woman and none had 25(OH)D or 24,25(OH)2D concentrations in the toxicity range or suggestive of mutations in the CYP24A1 gene. CaAlb was significantly higher in hypercalcemic cases compared to controls in T1 (2.44 (2.30-2.80) vs 2.37 (2.25-2.49) mmol/L) and T3 (2.63 (2.52-2.78) vs 2.46 (2.31-2.58) mmol/L). Serum P was higher among cases than controls in T3 (1.12 (0.16) vs 1.07 (0.18) mmol/L) but not in T1 (1.12 (0.18) and 1.12 (0.16) mmol/L). PTH in T3 was lower in cases (1.6 (1.6-2.8) vs 2.3 (2.1-2.8) pmol/L) but 1,25(OH)2D concentrations were similar. There were no significant group differences in serum 25(OH)D, free 25(OH)D, 24,25(OH)2D, Mg, Alb, Cr and eGFR. Regression analyses did not show significant differences between cases and controls in relationships between vitamin D metabolites and with PTH, except for the free 25(OH)D-PTH relationship and a higher free:total 25(OH)D ratio in cases at T1. In conclusion, most common causes of hypercalcemia were excluded in the majority of women. Hypercalcemic women had a relatively high serum 1,25(OH)2D concentration despite an appropriately suppressed PTH, suggestive of abnormal gestational adaptions.


Assuntos
Cálcio/sangue , Hipercalcemia/metabolismo , Complicações na Gravidez/metabolismo , Vitamina D/metabolismo , Adulto , Cálcio/metabolismo , Cálcio na Dieta/uso terapêutico , Creatinina/sangue , Feminino , Humanos , Hipercalcemia/sangue , Hipercalcemia/epidemiologia , Magnésio/sangue , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/metabolismo , Fosfatos/sangue , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/epidemiologia , Albumina Sérica/metabolismo , Suécia/epidemiologia , Vitamina D/sangue
8.
Malar J ; 19(1): 85, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32085712

RESUMO

BACKGROUND: Hypophosphatemia is common in severe infections including malaria. Previous studies suggested that serum phosphate concentrations correlate with temperature, but it is unclear whether the type of infection and other factors occurring during infection influence this association. Here relationships were investigated between serum phosphate levels, cause of fever, demographic, clinical and laboratory parameters. METHODS: Anonymized data were analysed from 633 adults with malaria or other febrile illness admitted to Northwick Park Hospital, London, UK. Univariable and multivariable generalized linear model analyses were performed to examine associations with serum phosphate levels. Interaction terms were included to investigate whether cause of fever (malaria vs other illness), malaria parasite species, or malaria severity influenced the association of other variables with phosphate. RESULTS: Hypophosphatemia was common in subjects with malaria (211/542 (39%)), and in other febrile illnesses (24/91 (26%)), however median phosphate levels did not differ significantly by diagnostic group, parasite species or severity of malaria. In all analyses, there were highly significant negative associations between serum phosphate and axillary temperature, and positive associations between serum phosphate and platelet count. There were no significant interactions between these variables and cause of fever, parasite species or severity of illness. Sodium and potassium concentrations were associated with serum phosphate in subjects with malaria and when data from all subjects was combined. CONCLUSION: Serum phosphate is consistently associated with temperature and platelet count in adults with diverse causes of fever. This may be a consequence of phosphate shifts from plasma into cells to support ATP generation for thermogenesis and platelet activation.


Assuntos
Temperatura Corporal , Malária Falciparum/metabolismo , Malária Vivax/metabolismo , Fosfatos/sangue , Adulto , Testes Diagnósticos de Rotina , Feminino , Humanos , Londres , Malária Falciparum/sangue , Malária Vivax/sangue , Masculino , Pessoa de Meia-Idade , Adulto Jovem
9.
PLoS One ; 15(1): e0227692, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31945095

RESUMO

BACKGROUND: Life-style interventions, including smoking cessation and weight control are of importance for managing future escalating prevalence of obesity. Smoking habits and obesity have jointly great impact on mortality, however mechanisms behind the effect and variables involved in the obesity paradox is still unknown. OBJECTIVES: This study examines risk factors for all-cause, cardiovascular, and cancer mortality in males and females with high cardiovascular risk, mediated by smoking habits, body mass index (BMI, kg/m2), and serum phosphate (S-P) levels. METHODS: Patients were admitted to the Vindeln Patient Education Center in groups of 30 for a four-week residential comprehensive program (114 hours) focusing on smoking cessation, stress reduction, food preferences and selections, and physical exercise. The follow-up, in years from 1984 to 2014 corresponds to 30 years. This study included 2,504 patients (1,408 females and 1,096 males). Cox regression analysis was used to assess mortality risk associated with smoking habits, low and high BMI, and low and high S-P levels. RESULTS: High BMI (>34,2 kg/m2), current smoking, type 2 diabetes mellitus (T2DM), high serum calcium (S-Ca), mmol/L and high systolic blood pressure (SBP, mmHg) were associated with all-cause mortality irrespective of sex. Former and current smoking females had a high all-cause mortality (adjusted hazard ratio [HR] 1.581; 95% CI 1.108-2.256, adjusted hazard ratio [HR] 1.935; 95% CI 1.461-2.562, respectively) while current smoking and high BMI increased risk for cardiovascular mortality (adjusted hazard ratio [HR] 3.505; 95% CI 2.140-5.740 and [HR] 1.536; 95% CI 1.058-2.231, respectively). Neither low nor high levels of S-P predicted all-cause, cardiovascular disease (CVD) and cancer mortality in males or females while low levels of S-P predicted all-cause mortality in smokers (adjusted hazard ratio [HR] 1.713; 95% CI 1.211-2.424). In non-smokers, low BMI (<27.6 kg/m2) was protecting and high BMI a risk for all-cause mortality. In males, ischemic heart disease (IHD), and low serum albumin (S-Alb) were associated with all-cause mortality. In females, an interaction between high BMI and smoking (HbmiSM) decreased the cardiovascular mortality (adjusted hazard ratio [HR] 0.410; 95% CI 0.179-0.937, respectively). CONCLUSIONS: High BMI and current smoking were associated with all-cause mortality in both males and females in the present high cardiovascular-risk cohort. In current smokers and non-smokers, T2DM and high S-Ca were associated with an increase in all-cause mortality, while low S-P was associated with all-cause mortality in smokers. Interaction between high BMI and smoking contribute to the obesity paradox by being protective for cardiovascular mortality in females.


Assuntos
Promoção da Saúde/métodos , Obesidade/mortalidade , Fosfatos/sangue , Fumar/mortalidade , Adulto , Índice de Massa Corporal , Estudos de Coortes , Feminino , Estilo de Vida Saudável , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/terapia , Fatores de Risco , Fumar/sangue , Fumar/terapia , Abandono do Hábito de Fumar , Suécia/epidemiologia , Programas de Redução de Peso
10.
J Bone Miner Metab ; 38(3): 405-411, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31897746

RESUMO

INTRODUCTION: Because aging is a predictor of renal insufficiency in the general population, renal function is a concern in postmenopausal patients undergoing treatment for osteoporosis. Although high serum phosphate concentration is a predictor of renal insufficiency, the effect of selective estrogen receptor modulator (SERM) on renal function and phosphate homeostasis remains to be established. MATERIALS AND METHODS: We administered 20 mg/day bazedoxifene to 48 postmenopausal osteoporotic women who had been taking alfacalcidol for ≥ 6 months, and assessed lumbar spine bone mineral density (LS-BMD), renal function (by calculating estimated glomerular filtration rate using serum cystatin-C levels [eGFRcys] [range 38.0-98.2 mL/min/1.73 m2]), and phosphate homeostasis. RESULTS: LS-BMD was significantly higher 6 months after the initiation of bazedoxifene administration. eGFRcys had increased by 3 months after initiation and was stable until 12 months. Serum phosphate gradually decreased after initiation, reaching statistical significance at 6 months. The changes in serum phosphate were also significant when the maximum tubular reabsorption rate of phosphate was normalized to glomerular filtration rate (TmP/GFR), indicating that bazedoxifene treatment reduces serum phosphate by increasing the urinary excretion of phosphate. The change in eGFRcys after the initiation of bazedoxifene was significantly negatively correlated with the change in serum phosphate, suggesting that a reduction in serum phosphate improves renal function. CONCLUSION: Bazedoxifene improves renal function, possibly by increasing renal phosphate excretion, in postmenopausal osteoporotic women without severe renal insufficiency.


Assuntos
Indóis/uso terapêutico , Rim/fisiopatologia , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/urina , Fosfatos/urina , Idoso , Densidade Óssea/efeitos dos fármacos , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Taxa de Filtração Glomerular/efeitos dos fármacos , Homeostase , Humanos , Indóis/farmacologia , Rim/efeitos dos fármacos , Modelos Lineares , Osteoporose Pós-Menopausa/sangue , Osteoporose Pós-Menopausa/fisiopatologia , Hormônio Paratireóideo/sangue , Fosfatos/sangue
11.
J Bone Miner Metab ; 38(1): 1-6, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31797064

RESUMO

Abnormal phosphate levels result in several pathological conditions such as rickets/osteomalacia and ectopic calcification indicating that there must be a system that regulates phosphate level within a narrow range. FGF23 has been shown to be an essential hormone regulating serum phosphate level. FGF23 binds to Klotho-FGF receptor complex to reduce serum phosphate level. Several reports suggested that FGF receptor is involved in the regulation of FGF23 production. It has been also shown that high extracellular phosphate can activate several intracellular signaling pathways. However, it has been unclear whether and how phosphate regulates FGF23 production in vivo. Our recent results indicate that high extracellular phosphate directly activates FGF receptor 1 and the downstream intracellular signaling enhances FGF23 production. Thus, there is a negative feedback system for the regulation of serum phosphate level involving FGF receptor and FGF23. We propose that FGF receptor works at least as one of phosphate sensors in the maintenance of serum phosphate level.


Assuntos
Fosfatos/sangue , Animais , Fatores de Crescimento de Fibroblastos/metabolismo , Humanos , Modelos Biológicos , Transdução de Sinais
13.
Am J Kidney Dis ; 75(2): 235-244, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31668375

RESUMO

RATIONALE & OBJECTIVE: The pathogenesis of disordered mineral metabolism in chronic kidney disease (CKD) is largely informed by cross-sectional studies of humans and longitudinal animal studies. We sought to characterize the longitudinal evolution of disordered mineral metabolism during the course of CKD. STUDY DESIGN: Retrospective analysis nested in a cohort study. SETTING & PARTICIPANTS: Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study who had up to 5 serial annual measurements of estimated glomerular filtration rate, fibroblast growth factor 23 (FGF-23), parathyroid hormone (PTH), serum phosphate, and serum calcium and who subsequently reached end-stage kidney disease (ESKD) during follow-up (n = 847). EXPOSURE: Years before ESKD. OUTCOMES: Serial FGF-23, PTH, serum phosphate, and serum calcium levels. ANALYTICAL APPROACH: To assess longitudinal dynamics of disordered mineral metabolism in human CKD, we used "ESKD-anchored longitudinal analyses" to express time as years before ESKD, enabling assessments of mineral metabolites spanning 8 years of CKD progression before ESKD. RESULTS: Mean FGF-23 levels increased markedly as time before ESKD decreased, while PTH and phosphate levels increased modestly and calcium levels declined minimally. Compared with other mineral metabolites, FGF-23 levels demonstrated the highest rate of change (velocity: first derivative of the function of concentration over time) and magnitude of acceleration (second derivative). These changes became evident approximately 5 years before ESKD and persisted without deceleration through ESKD onset. Rates of changes in PTH and phosphate levels increased modestly and without marked acceleration around the same time, with modest deceleration immediately before ESKD, when use of active vitamin D and phosphate binders increased. LIMITATIONS: Individuals who entered the CRIC Study at early stages of CKD and who did not progress to ESKD were not studied. CONCLUSIONS: Among patients with progressive CKD, FGF-23 levels begin to increase 5 years before ESKD and continue to rapidly accelerate until transition to ESKD.


Assuntos
Densidade Óssea/fisiologia , Cálcio/sangue , Fosfatos/sangue , Insuficiência Renal Crônica/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos Transversais , Progressão da Doença , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Minerais/metabolismo , Hormônio Paratireóideo/sangue , Estudos Prospectivos , Adulto Jovem
14.
Nephrology (Carlton) ; 25(1): 22-28, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31081186

RESUMO

AIM: This study aimed to assess the relationship between admission Calcium-phosphate (CaP) and in-hospital mortality in hospitalized patients. METHODS: All adult hospitalized patients who had both admission serum calcium and phosphate levels available between years 2009 and 2013 were enrolled. Admission CaP was categorized based on its distribution into six groups (<21, 21-<27, 27-<33, 33 39, 39-<45 and ≥45 mg2 /dL2 ). Multivariate logistic regression was used to assess the association between admission CaP and in-hospital mortality, using the CaP of 27-<33 mg2 /dL2 as the reference group. RESULTS: Abut 14 772 patients were included in the analysis. The association between CaP and in-hospital mortality was U-shaped with the lowest in-hospital mortality in CaP of 27-<33 mg2 /dL2 . After adjusting for potential confounders, both CaP <21 and ≥39 mg2 /dL2 were associated with higher in-hospital mortality. Subgroup analysis demonstrated that the highest in-hospital mortality risk in both chronic kidney disease (CKD) and non-CKD patients occurred when CaP ≥ 45 mg2 /dL2 . CONCLUSION: CaP levels on admission were associated with in-hospital mortality. Highest mortality risk was observed in hospitalized patients with admission CaP of ≥45 mg2 /dL2 in both CKD and non-CKD patients.


Assuntos
Cálcio/sangue , Mortalidade Hospitalar , Hospitalização , Pacientes Internados , Fosfatos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
15.
J Clin Neurosci ; 71: 26-31, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31859176

RESUMO

An increased serum phosphate (P) level is common in acromegaly patients, however, the relationships among P, growth hormone (GH), insulin-like growth factor 1 (IGF-1) and disease status remain unknown. To reveal these relationships, we examined the association of P with comprehensive clinical data. We measured the serum P, calcium, GH, oral glucose tolerance test-GH (OGTT-GH), IGF-1, and insulin-like growth factor binding protein-3 (IGBP-3) levels in 103 acromegaly patients. SAGIT® was used to assess the disease status comprehensively. Spearman's rank correlation coefficient was obtained to evaluate the associations among the above parameters. Stepwise multiple linear regression analysis was performed to investigate factors independently associated factors with the SAGIT scores. The area under the receiver operating characteristic curve (AUCROC) was used to evaluate the efficacy of the percentage change in the serum phosphate level in predicting remission in patients with postoperatively discordant GH and IGF-1 levels. Hyperphosphatemia was found in 68.9% of patients at baseline. The serum P level was higher in the non-remission group, but no correlation was found between hyperphosphatemia and remission. We revealed a significant correlation between the P level and SAGIT® score in patients both preoperatively (r = 0.659, p = 0.000) and 1-year postoperatively without remission patients (r = 0.534, p = 0.027). All biochemical levels decreased significantly postoperatively, and the GH and OGTT-GH levels achieved early stability (1 month); however, the P, IGF-1 and IGBP-3 levels showed a gradual decline. A percentage change in P of -8.12% is recommended as a cut-off value for predicting remission in patients with postoperatively discordant GH and IGF-1 levels. As a metabolic product which affected by the GH/IGF-1 axis, serum P appears to more closely reflect the comprehensive disease status in acromegaly. When the GH and IGF-1 levels are discordant during follow-up, perioperative change in the P level may be a potential predictor of remission.


Assuntos
Acromegalia/sangue , Fosfatos/sangue , Acromegalia/etiologia , Adenoma/sangue , Adenoma/complicações , Adulto , Feminino , Teste de Tolerância a Glucose , Adenoma Hipofisário Secretor de Hormônio do Crescimento/sangue , Adenoma Hipofisário Secretor de Hormônio do Crescimento/complicações , Hormônio do Crescimento Humano/sangue , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Pessoa de Meia-Idade
16.
Br J Hosp Med (Lond) ; 80(12): C180-C183, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31822187

RESUMO

Chronic kidney disease-mineral bone disorder is typically seen in patients with advanced chronic kidney disease. It is managed primarily by renal physicians, but non-renal physicians are also likely to encounter patients undergoing treatment for this condition in both inpatient and outpatient settings so a basic understanding of the principles may be helpful. This article covers the fundamentals of the pathophysiology, diagnosis and treatment of chronic kidney disease-mineral bone disorder.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/fisiopatologia , Adulto , Cálcio/sangue , Doenças Cardiovasculares/epidemiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/epidemiologia , Distúrbio Mineral e Ósseo na Doença Renal Crônica/terapia , Humanos , Fosfatos/sangue , Diálise Renal , Índice de Gravidade de Doença
17.
Int J Med Sci ; 16(12): 1583-1592, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839746

RESUMO

Renal osteodystrophy (ROD) represents bone disorders related to chronic kidney disease (CKD) and several bone biomarkers are used clinically to predict ROD in CKD and hemodialysis (HD) patients. Serum albumin associates with inflammation other than nutritional status in these patients. Chronic inflammation is proved to relate with bone loss, however, the influence of hypoalbuminemia on bone biomarkers is still unclear. In this study, we evaluated the pattern of bone biomarker changes and further studied the influence of hypoalbuminemia on these biomarkers. A total of 300 maintenance HD patients were evaluated and 223 HD patients were included in the study. The patients were grouped according to serum parathyroid hormone (PTH) levels (PTH ≤150 pg/mL, PTH 150-300 pg/mL, PTH 300-600 pg/mL and PTH >600 pg/mL). Bone biomarkers and inflammatory markers were measured and their relation with PTH levels was determined. Significantly increased interleukin-6 (IL-6) and lower albumin levels were noted among PTH>600 pg/mL group. Bone turnover markers were significantly higher in PTH >600 pg/mL group (p< 0.05). Hypoalbuminemia significantly increased the fibroblast growth factor-23 (FGF-23) and procollagen type 1N-terminal propeptide (P1NP) in PTH ≤150 pg/mL, PTH 150-300 pg/mL, PTH 300-600 pg/mL groups, whereas no such relation was noted among PTH> 600 ng/dL group. In conclusion, hypoalbuminemia represents a chronic inflammation which differently relates to bone turnover markers according to serum PTH levels in SHPT patients. Thus, serum albumin measurement should be considered in determining bone disorders among these patients.


Assuntos
Distúrbio Mineral e Ósseo na Doença Renal Crônica/sangue , Hiperparatireoidismo/sangue , Hipoalbuminemia/sangue , Inflamação/sangue , Hormônio Paratireóideo/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Remodelação Óssea/genética , Distúrbio Mineral e Ósseo na Doença Renal Crônica/complicações , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Humanos , Hiperparatireoidismo/complicações , Hiperparatireoidismo/patologia , Hipoalbuminemia/complicações , Hipoalbuminemia/patologia , Inflamação/complicações , Inflamação/patologia , Interleucina-6/sangue , Falência Renal Crônica , Masculino , Pessoa de Meia-Idade , Fosfatos/sangue , Diálise Renal/efeitos adversos , Albumina Sérica/metabolismo
18.
Pol J Vet Sci ; 22(4): 647-652, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31867923

RESUMO

The aim of this study was to determine whether the serum concentration of the phosphate (Pi) and the Ca x P value correlate with the IRIS stage of chronic kidney disease (CKD) in cats and, thus, whether they can be used as markers of the disease progression. Another aim was to assess whether the concentration of Ca in blood needs to be corrected based on the albumin concentration. The study was performed on 165 cats divided into five groups: the healthy group - C and study groups: I, II, III and IV with cats assigned to the groups based on the IRIS scale. Blood was collected from all the animals. The product of Ca x Pi, Cacorr and the product of Cacorrx Pi were calculated based on the obtained results. Despite no differences between groups I-III, there was a clear upward trend in the Pi concentration, in the Ca x Pi and in the Cacorr x Pi with CKD progression. In group IV, the Pi concentration and the Ca x Pi as well as the Cacorr x Pi value were significantly higher than the other groups. The concentration of Ca and its albumin-corrected serum values did not differ significantly. The serum concentration of Pi and the Ca x P product cannot be used as indicators of CKD progression in cats, but they may be used as additional elements in the diagnosis of stage IV CKD. The results also suggest that the serum calcium concentrations do not need to be albumin-corrected in cats.


Assuntos
Doenças do Gato/sangue , Fosfatos/sangue , Insuficiência Renal Crônica/veterinária , Animais , Biomarcadores , Cálcio/sangue , Gatos , Feminino , Humanos , Masculino , Propriedade , Insuficiência Renal Crônica/sangue
19.
J. bras. nefrol ; 41(4): 481-491, Out.-Dec. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1056601

RESUMO

Abstract Introduction: It is unclear whether residual renal function (RRF) in dialysis patients can attenuate the metabolic impact of the long 68-hour interdialytic interval, in which water, acid, and electrolyte accumulation occurs. Objective: to evaluate serum electrolyte levels, water balance, and acid-base status in dialytic patients with and without RRF over the long interdialytic interval (LII). Methodology: this was a single-center, cross-sectional, and analytical study that compared patients with and without RRF, defined by diuresis above 200 mL in 24 hours. Patients were weighed and serum samples were collected for biochemical and gasometric analysis at the beginning and at the end of the LII. Results: 27 and 24 patients with and without RRF were evaluated, respectively. Patients without RRF had a higher increase in serum potassium during the LII (2.67 x 1.14 mEq/L, p < 0.001), reaching higher values at the end of the study (6.8 x 5.72 mEq/L, p < 0.001) and lower pH value at the beginning of the interval (7.40 x 7.43, p = 0.018). More patients with serum bicarbonate < 18 mEq/L (50 x 14.8%, p = 0.007) and mixed acid-base disorder (57.7 x 29.2%, p = 0.042), as well as greater interdialytic weight gain (14.67 x 8.87 mL/kg/h, p < 0.001) and lower natremia (137 x 139 mEq/L, p = 0.02) at the end of the interval. Calcemia and phosphatemia were not different between the groups. Conclusion: Patients with RRF had better control of serum potassium, sodium, acid-base status, and volemia throughout the LII.


Resumo Introdução: Não se sabe ao certo se a função renal residual (FRR) de pacientes dialíticos pode atenuar o impacto metabólico do maior intervalo interdialítico (MII) de 68 horas, no qual ocorre acúmulo de volume, ácidos e eletrólitos. Objetivo: Avaliar os níveis séricos de eletrólitos, balanço hídrico e status ácido-básico de pacientes dialíticos com e sem FRR ao longo do MII. Metodologia: Tratou-se de estudo unicêntrico, transversal e analítico, que comparou pacientes com e sem FRR, definida como diurese acima de 200 mL em 24 horas. Para tal, os pacientes foram pesados e submetidos à coleta de amostras séricas para análise bioquímica e gasométrica no início e fim do MII. Resultados: Foram avaliados 27 e 24 pacientes com e sem FRR, respectivamente. Pacientes sem FRR apresentaram maior aumento de potássio sérico durante o MII (2,67 x 1,14 mEq/L, p < 0,001) atingindo valores mais elevados no fim (6,8 x 5,72 mEq/L, p < 0,001); menor valor de pH no início do intervalo (7,40 x 7,43, p = 0,018), maior proporção de pacientes com bicarbonato sérico < 18 mEq/L (50 x 14,8 %, p = 0,007) e distúrbio ácido-básico misto (70,8 x 42,3 %, p = 0,042), além de maior ganho de peso interdialítico (14,67 x 8,87 mL/kg/h, p < 0,001) e menor natremia (137 x 139 mEq/L, p = 0,02) no fim do intervalo. A calcemia e fosfatemia não foram diferentes entre os grupos. Conclusão: Pacientes com FRR apresentaram melhor controle dos níveis séricos de potássio, sódio, status ácido-básico e da volemia ao longo do MII.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Equilíbrio Hidroeletrolítico/fisiologia , Diálise Renal/efeitos adversos , Insuficiência Renal/sangue , Rim/fisiopatologia , Fosfatos/sangue , Potássio/sangue , Sódio/sangue , Desequilíbrio Ácido-Base/fisiopatologia , Bicarbonatos/sangue , Ganho de Peso , Cálcio/sangue , Estudos Transversais , Progressão da Doença , Insuficiência Renal/fisiopatologia , Insuficiência Renal/urina , Insuficiência Renal/terapia , Rim/metabolismo , Rim/química , Testes de Função Renal/métodos
20.
J Investig Med High Impact Case Rep ; 7: 2324709619895162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31850815

RESUMO

Tumor-induced osteomalacia is a rare hypophosphatemic disease caused by unregulated production of fibroblast growth factor 23 by a tumor, thereby inducing renal phosphate wasting and inhibiting appropriate increase of calcitriol production. Symptoms of tumor-induced osteomalacia, including muscle weakness, bone pain, and pathologic fractures, are nonspecific and warrant further workup. We report the case of a 50-year-old African American female with no known psychiatric illness who was admitted after a failed suicide attempt provoked by severe bone pain. She had been treated for fibromyalgia and hypophosphatemic rickets at other facilities with no improvement. The findings of profound renal phosphate wasting initiated further evaluation, which revealed an elevated fibroblast growth factor 23 level and a right proximal fibular mesenchymal tumor on octreotide scintigraphy. Magnetic resonance imaging confirmed the findings of a solid intramuscular tumor corresponding to the octreotide avid lesion. After wide excision of the tumor, serum phosphate and parathyroid hormone levels began to normalize. This case highlights the importance of extensively investigating the cause of bone pain, weakness, and fatigue in patients without a family history of hypophosphatemia or bone disorders. The aforementioned symptoms may precede recurrent pathological fractures, and a thorough workup ensures that a diagnosis of tumor is not delayed or overlooked, as tumor resection confers a favorable prognosis and dramatic increase in the quality of life for patients.


Assuntos
Fatores de Crescimento de Fibroblastos/sangue , Neoplasias de Tecido Conjuntivo/diagnóstico , Síndromes Paraneoplásicas/diagnóstico , Tentativa de Suicídio/psicologia , Diagnóstico Tardio/psicologia , Feminino , Fibromialgia/etiologia , Humanos , Hipofosfatemia/etiologia , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Neoplasias de Tecido Conjuntivo/sangue , Neoplasias de Tecido Conjuntivo/complicações , Dor/etiologia , Síndromes Paraneoplásicas/sangue , Síndromes Paraneoplásicas/complicações , Fosfatos/sangue , Cintilografia , Raquitismo Hipofosfatêmico/etiologia
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